1. Field of the Invention
This invention provides a convenient process for isolating syn-7-(2-amino-4-thiazolyl) (methoxyimino) acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid by formation of crystalline cyclic ether solvates.
Prior Art
U.S. Pat. No. 4,152,432, of Roussel Uclaf, discloses syn-7-(2-amino-4-thiazolyl) (methoxyimino) acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid, an antibiotic cephalosporin hereinafter called compound A. The compound is an important member of a class of (2-amino-4-thiazolyl) (methoxyimino) cephalosporin compounds which have appeared in the literature before, and are now established as an important group of antibiotics.
The Roussel patent shows formic acid and ethanol solvates of syn-7-(2-amino-4-thiazolyl) (methoxyimino)acetamido-3-acetoxymethyl-3-cephem-4-carboxylic acid, which solvates are used in the crystallization of the compounds.
Solvates of cephalosporin antibiotics have frequently been observed and noted in the literature. For example, U.S. Pat. No. 3,925,372, of Chauvette, shows the preparation of a dimethylformamide solvate of 7-(D-phenylglycylamido)-3-chloro-3-cephem-4-carboxylic acid.
Solvates, however, are notoriously unpredictable substances. One can not predict what cephalosporin compounds will form solvates, nor the solvents with which solvates may be formed. It is noticeable that various salts, esters, and amino-protected derivatives of compound A have often been treated with cyclic ethers in the literature, but no prior worker has observed the solvates which have now been discovered to be formed with the unprotected acid form of the compound. See, for example, U.S. Pat. Nos. 4,152,432 and 4,098,888, and South African Pat. No. 77/2030.